A Dose-Ranging Study of the DPP-IV Inhibitor PF-734200 Added to Metformin in Subjects With Type 2 Diabetes (original) (raw)

Exp Clin Endocrinol Diabetes 2011; 119(7): 401-407
DOI: 10.1055/s-0031-1273737

Article

S. G. Terra1 , V. Somayaji1 , S. Schwartz2 , A. J. Lewin3 , J. G. Teeter1 , H. Dai1 , T. T. Nguyen1 , R. A. Calle1

1Pfizer Global Research and Development, New London, Connecticut, USA
2Diabetes and Glandular Disease Research Associates, San Antonio, Texas, USA
3National Research Institute, Los Angeles, California, USA

Further Information

Publication History

received 04.10.2010 first decision 07.01.2011

accepted 17.02.2011

Publication Date:
06 April 2011 (online)

Abstract

The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin. Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were randomized to placebo or PF-734200 2 mg, 5 mg, 10 mg, or 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline and week 12. A total of 301 subjects were treated. At week 12, PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A1C (HbA1c) compared with placebo. The mean (95% confidence interval) placebo-adjusted changes in HbA1c were −0.31% (−0.70 to 0.08), −0.74% (−1.12 to −0.36), −0.70% (−1.02 to −0.38), and −0.75% (−1.07 to −0.43) for the 2 mg, 5 mg, 10 mg, and 20 mg doses, respectively. PF-734200 20 mg significantly reduced glucose area under the curve following MMTT (−12.8% [−22.9 to −2.7]; p=0.003) compared with placebo. The reductions observed with other doses were not statistically significant. PF-734200 was safe and well tolerated at all doses tested when added to metformin. PF-734200 safely and effectively lowered HbA1c in subjects receiving metformin. The 20 mg dose provided the greatest improvements in post-prandial glucose.

Key words

diabetes - dipeptidyl peptidase-4 - DPP-IV inhibitor - PF-734200 - incretins

1 Clinical Trials Registration Number NCT00473525. Data in this paper were presented in abstract form at the 69 th Scientific Sessions of the American Diabetes Association; June 5 – 9, 2009; New Orleans, Louisiana, USA.

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Correspondence

S. G. Terra

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